Product Description

Heprasil® is thiol-modified hyaluronic acid with thiol-modfied heparin and is a component of the HyStem® hydrogel kit. Hyaluronic acid is a major constituent of native extracellular matrix (ECM). Heparin is also present in the ECM as heparan sulfate. Most cells do not attach to Heprasil-only hydrogels. Heprasil must be used in conjunction with Gelin-S® or ECM proteins such as laminin, collagen, or fibronectin for most 3-D cell culture and tissue-engineering applications.

Gelation
Reconstituted Heprasil remains liquid at 15 to 37°C. Without a crosslinker, Heprasil will form a hydrogel via disulfide bond formation; however, the gelation time is over twenty-four hours. If Extralink® is used to crosslink the Heprasil, the gelation time is about twenty minutes with no low-temperature or low-pH steps. Diluting Heprasil with phosphate-buffered saline (PBS) or cell-culture medium can increase its gelation time.

Directions for Use

Heprasil® is prepared by dissolving the lyophilized solid in the DG Water (or any sterile, degassed, deionized water). When re-constituted, it will be in 1x phosphate buffered saline (PBS), pH ~7.4. The amount of DG Water used for dissolution will depend on the vial.

Heprasil® should be prepared in the following manner:

  1. Allow the Heprasil® vial to come to room temperature.
  2. Under aseptic conditions, using a syringe and needle, add to the vial the amount of DG Water indicated on the label.
  3. Place the vial horizontally on a rocker or shaker. It will take <40 minutes for the solids to fully dissolve. Warming to 37°C and/or gently vortexing will speed up dissolving time. Solutions will be clear and slightly viscous.
  4. Use with Extralink® or Extralink-Lite to form a hydrogel.
  5. Typically, crosslinkers are used in a 1:4 volume ratio with the polymer (i.e. 1.0 mL of Heprasil is crosslinked with 0.25 mL Extralink-Lite; or 0.5 mL Heprasil combined with 0.5 mL Gelin-S® is crosslinked with 0.25 mL Extralink).
  6. Note: The gelation time will be shorter for gels not incorporating Gelin-S. Hydrogels made using only Heprasil will not support cell attachment. Use with Gelin-S for cell attachment.

Product References

References for HyStem®:

Gaetani, R., et al. (2015) Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials 61: 339-348. PMID: 17335875.

Prestwich, G.D., et al. (2007) 3-D culture in synthetic extracellular matrices: new tissue models for drug toxicology and cancer drug discovery. Adv Enzyme Regul 47: 196-207. PMID: 17335875.

Shu, X.Z., et al. (2006) Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering. J Biomed Mater Res A 79: 901-912. PMID: 16941590.

Shu, X.Z., et al. (2003) Disulfide-crosslinked hyaluronan-gelatin hydrogel films: a covalent mimic of the extracellular matrix for in vitro cell growth. Biomaterials 24: 3825-3834. PMID: 12818555.

S. Cai, et al. (2005) Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor.Biomaterials, 26, 6054-6067.

D. B. Pike, et al. (2006) Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. Biomaterials, 27, 5242–5251.

G. D. Prestwich, et al. (2007) 3-D Culture in Synthetic Extracellular Matrices: New Tissue Models for Drug Toxicology and Cancer Drug Discovery. invited, Adv. Enz. Res., in press (2007).

X. Z. Shu, et al, (2006) Synthesis and Evaluation of Injectable, In Situ Crosslinkable Synthetic Extracellular Matrices (sECMs) for Tissue Engineering. J. Biomed Mater. Res. A, 79A(4), 901-912.

Shu, X.Z., et al. (2004) In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 25: 1339-1348. PMID: 14643608. 

Mehra, T.D., et al. (2006) Molecular stenting with a crosslinked hyaluronan derivative inhibits collagen gel contraction. J Invest Dermatol 126: 2202-2209. PMID: 16741511. 

Shu, X.Z., et al. (2004) Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel. J Biomed Mater Res A 68: 365-375. PMID: 14704979. 

Ghosh, K., et al. (2007) Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties. Biomaterials 28: 671-679. PMID: 17049594.

Product Certificate of Analysis

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Product Disclaimer

This product is for R&D use only and is not intended for human or other uses. Please consult the Material Safety Data Sheet for information regarding hazards and safe handling practices.